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. 2014 Aug;171(8):881-8.
doi: 10.1176/appi.ajp.2014.13121581.

Decreased prefrontal cortical dopamine transmission in alcoholism

Rajesh Narendran, Neale Scott Mason, Jennifer Paris, Michael L Himes, Antoine B Douaihy, W Gordon Frankle

Decreased prefrontal cortical dopamine transmission in alcoholism

Rajesh Narendran et al. Am J Psychiatry. 2014 Aug.

Abstract

Objective: Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence.

Method: To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine.

Results: Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe.

Conclusions: The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

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Figures

Figure 1
Figure 1
shows the lack of difference in D2/3 receptor availability in cortical regions of interest in alcohol dependent subjects (black bars) compared to healthy controls (white bars). MTL: medial temporal lobe, DLPFC: dorsolateral prefrontal cortex, OFC: orbital frontal cortex, MPFC: medial prefrontal cortex, ACC: anterior cingulate cortex, TEMP: temporal cortex, PAR: parietal cortex, and OCC: occipital cortex
Figure 2
Figure 2
shows [11C]FLB 457 BPND under baseline (white bars) and post-amphetamine (black bars) conditions in healthy controls (left panel) and alcohol dependent subjects (right panel). Amphetamine led to a significant decrease in [11C]FLB 457 BPND in healthy controls, but not in alcohol dependence (* represents p< 0.05, following the false discovery rate correction for multiple comparisons). MTL: medial temporal lobe, DLPFC: dorsolateral prefrontal cortex, OFC: orbital frontal cortex, MPFC: medial prefrontal cortex, ACC: anterior cingulate cortex, TEMP: temporal cortex, PAR: parietal cortex, and OCC: occipital cortex
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References

    1. Brozoski TJ, Brown RM, Rosvold HE, Goldman PS. Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science. 1979;205(4409):929–32. - PubMed
    1. Sawaguchi T, Goldman-Rakic PS. D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science. 1991;251(4996):947–50. - PubMed
    1. Bickel WK, Jarmolowicz DP, Mueller ET, Gatchalian KM, McClure SM. Are executive function and impulsivity antipodes? A conceptual reconstruction with special reference to addiction. Psychopharmacology (Berl) 2012;221(3):361–87. - PMC - PubMed
    1. Longmore BE, Knight RG. The effect of intellectual deterioration on retention deficits in amnesic alcoholics. J Abnorm Psychol. 1988;97(4):448–54. - PubMed
    1. Goldman MS. Cognitive impairment in chronic alcoholics. Some cause for optimism. Am Psychol. 1983;38(10):1045–54. - PubMed

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